Chemical and computer probing of RNA structure.

Ribonucleic acids (RNAs) are one of the most important types of biopolymers. RNAs play key roles in the storage and multiplication of genetic information. They are important in catalysis and RNA splicing and are the most important steps of translation.

A compilation of composite regulatory elements affecting gene transcription in vertebrates.

Over the past years, evidence has been accumulating for a fundamental role of protein-protein interactions between transcription factors in gene-specific transcription regulation. Many of these interactions run within composite elements containing binding sites for several factors. We have selected 101 composite regulatory elements identified experimentally in the regulatory regions of 64 genes of vertebrates and of their viruses and briefly described them in a compilation.

Eukaryotic promoter recognition by binding sites for transcription factors.

A method for identification of eukaryotic promoters by localization of binding sites for transcription factors has been suggested. The binding sites for a range of transcription factors have been found to be distributed unevenly. Based on these distributions, we have constructed a weight matrix of binding site localization.

Identification of cDNA sequences by specific oligonucleotide sets. Computer tool and application.

A computer tool has been developed for revealing sets of oligonucleotides invariant for isofunctional families of DNA (RNA) and for using these in functional identification of nucleotide sequences. The tool allows one to: build up vocabularies of invariant oligonucleotides for the families of isofunctional nucleotide sequences; assess significance of the vocabularies; identify nucleotide sequences with the vocabularies of invariant oligonucleotides; determine the most effective identification parameters to minimize first and second type errors; assess the efficiency of identification of individual isofunctional families with the oligonucleotide vocabularies; determine the evolutionary characteristics of the families of isofunctional sequences on which vocabulary volume depends. Based on the system mentioned, we have analyzed a total of 322 protein-encoding gene families and have built up sets of invariant oligonucleotides, or again, oligonucleotide vocabularies that are characteristic of gene families and subfamilies.

Computer tool FUNSITE for analysis of eukaryotic regulatory genomic sequences.

We present the computer tool FUNSITE for description and analysis of regulatory sequences of eukaryotic genomes. The tool consists of the following main parts: 1) An integrated database for genomic regulatory sequences. The integrated database was designed on the basis of the databases TRANSFAC (Wingender 1994) and TRRD (Kel et al.

Construction of a generalized consensus matrix for recognition of vertebrate pre-mRNA 3'-terminal processing sites.

Using a set of sequences of 63 cleavage/polyadenylation sites of vertebrate pre-mRNA, a generalized consensus matrix was constructed. The elements of the matrix were the absolute frequencies of oligonucleotides of length l at the ith position of sites. The cleavage point of each site was assigned the same position number.

Can three-dimensional contacts in protein structures be predicted by analysis of correlated mutations?

A method has been developed to detect pairs of positions with correlated mutations in protein multiple sequence alignments. The method is based on reconstruction of the phylogenetic tree for a set of sequences and statistical analysis of the distribution of mutations in the branches of the tree. The database of homology-derived protein structures (HSSP) is used as the source of multiple sequence alignments for proteins of known three-dimensional structure.

SITEVIDEO: a computer system for functional site analysis and recognition. Investigation of the human splice sites.

We developed the computer system SITEVIDEO for analysis and recognition of the functional sites in DNA and RNA molecules. It reveals contextual features essential for site function and thus enable the user to design efficient methods for recognition of the functional sites. We mainly considered only quantitative characteristics reflecting the uneven distribution of oligonucleotides in the sequences of functional sites of interest.

Fast, statistically based alignment of amino acid sequences on the base of diagonal fragments of DOT-matrices.

We present a new pairwise alignment algorithm that uses iterative statistical analysis of homologous subsequences. Apart from the classical conversion of the DOT-matrix characteristic of the Needleman-Wunsch algorithm (NW), we used only those matrix elements that corresponded to the most non-random subsequence homologies. The most reliable elements of the DOT-matrix are written to the compact competition matrices.

Somatic hypermutagenesis in immunoglobulin genes. II. Influence of neighbouring base sequences on mutagenesis.

A new approach for the analysis of hotspots of mutations is described. It is based on the classification of hotspot site sequences. Using this approach, the consensuses RGYW and TAA of hotspot sites were revealed in the V gene.

[Precise recognition method of structure-function determinants of protein molecules].

This paper is devoted to a computer system designed for formal description and knowledge about protein structural-functional determinants. Structural-functional determinant is a region of amino acid sequence with certain structural, functional or evolutionary properties specific for each class of macromolecules. Here the problem is solved by a special method which allows to design programs able to distinguish these structural-functional determinants.

Somatic hypermutagenesis in immunoglobulin genes. I. Correlation between somatic mutations and repeats. Somatic mutation properties and clonal selection.

Based on the analysis of some immunoglobulin V-gene sequences, somatic mutations are assumed to occur by correction of complementary violations in heteroduplexes formed by direct or inverted repeats. Correlation between somatic mutations and repeats is investigated by a statistical weights method in 323 somatic substitutions in 14 V-genes. Assuming absence of correlation, the probability of observing data in the sample would be very low (0.

[Theoretical analysis of mechanisms of spontaneous and induced mutations in DNA based on repeated sequences].

Mechanisms of spontaneous and chemically induced point mutations' emergence in DNA have theoretically been investigated using the statistical weight method. We have analysed 12 nucleotide sequences containing 95 point spontaneous mutations and 3 sequences comprising 30 mutations induced by such mutagens as 4'-hydroxymethyl-4,5',8-threemethylpsoralene, natrium bisulfite, hydroxylamine. The possibility of occurrence of point mutations by repair correction of heteroduplexes formed via mispairing of imperfect direct and inverted repeats in DNA has been studied.

[Evolution of Alu repeats: dynamics of distribution in genome].

A mathematical model of evolutionary dynamics of Alu repeats' number in the human genome has been worked out. The model permitted us to observe the dynamics of propagation of Alu repeats within the genome and to evaluate such important parameters of the process mentioned as the rates of transposition (insertion of new copies into the genome) and excision of repeats. The peculiarities of the control of Alu repeats' number in the genome have been discussed, based on the data obtained.

[Phylogenetic analysis of genes of the influenza virus. Relationship between adaptability and neutrality].

Detailed phylogenetic analysis of the gene family of hemagglutinin H3 of influenza A-type virus was fulfilled, taking into account the domain structure of protein and positions of antigen determinants. The densities of distribution of fixed synonimic replacements between domains HA1 and HA2 were shown to be actually equal (rho (HA1) = rho (HA2], and those of nonsynonimic ones to be unequal: their ratios were rho (HA1): rho (HA2) = 2.8 for nonepidemic branches, and rho (HA1): rho (HA2) = 7.

[A phylogenetic analysis of genes of the influenza virus. Phylogenetic trees and fixation rates].

The phylogenetic trees of influenza virus genes of hemagglutinins, neuraminidases, and of NS genes were composed. Considering properties of synonimic replacements to be neutral and their rates constant at each tree, the dates of ancestor branch points were calculated, and the rates of fixation of synonimic (Ks) and non-synonimic (Kns) replacements estimated. The epidemic branches were mostly shown to be "deadlocks", non-epidemic ones being internal or "roots.

[tRNA as a possible primer for the initiation of reverse transcription of dispersed repeats Alu, B1, B2 and L1].

The contextual analysis of the primary structures of 28 various dispersed repeats Alu, B1, B2 and L1 (Kpn1) of primates and rodent genomes has been carried out to search for the regions complementary to the 3'-ends of the known at present tRNA of these organisms. It has been shown that the abundance of the investigated repeats contain the regions revealing marked and statistically non-random complementarity to the 3'-end of at least one of the tRNA considered. Taking into account the retroviruses replication model known from literature these revealed regions are considered as potential primer-binding sites for the initiation of reverse transcription of the mentioned repeats or more long DNA fragments containing them.

[Somatic hypermutagenesis in immunoglobulin genes. I. Connection of somatic mutations with repeats. A statistical weighting method].

Based on the analysis of a number of immunoglobulin genes' nucleotide sequences, it has been suggested, that somatic mutations emerge by means of imperfect duplexes correction, formed by mispairing of complementary regions of direct and inverted repeats. In the present work provides new data, confirming this mechanism of somatic hypermutagenesis. It has been shown that the presented sample of V- and J-segments of immunoglobulin genes is abundant in nonrandom imperfect direct repeats and complementary palindromes.

[Theoretical analysis of the DNA duplication mechanisms in the prokaryotic genomes on the basis of repeats].

In the present work a theoretical analysis of the molecular mechanisms on duplications emergence in the genomes of prokaryotes on the basis of direct repeats has been carried out. The correlations obtained have shown, that the duplication rate depends on such parameters as the distance between repeated regions, repeats nucleotide composition and the number of homology damages in them. It has been revealed that the rate of duplications decreases more readily than the deletion rate upon the growth of the distance between the repeats.

[Distribution of Alu repeats along the human genome: formation of clusters and features of insertion regions].

The contextual analysis of nucleotide sequences of 22 Alu repeats arrangement regions in the human genome has been carried out and some of their peculiarities have been revealed. In particular, the occurrence of marked and statistical non-random homology between the repeats and the regions of their integration has been shown. A mechanism of choosing the Alu repeats insertion regions in the genome has been suggested taking into account these peculiarities.

[Theoretical analysis of mechanisms of occurrence of DNA deletions in prokaryotic genomes based on direct repeats].

In the present work a mechanism of deletions emergence on the basis of complementary DNA regions mispairing of direct repeats has been investigated theoretically. A quantitative dependence of the rates of deletions emergence on such parameters of the flanking repeats as the nucleotide composition of repeats, the number of homology damages and the distance between repeated regions has been constructed. It has been proved, that using this relationship one can reliably evaluate the total rates of deletions emergence in the lacI gene sequence of E.

[Statistical evidence for the correlation of DNA deletions in prokaryotic genomes with direct repeats].

In the present work a computer analysis of deletion localization in the sequence of the E. coli lacI gene has been carried out by the statistical weight method. Reliable statistical correlation of the deletions location sites with the arrangement of the most perfect direct repeats revealing the shortest distance between repeated fragments has been shown.